HOPE-B: Trial of AMT-061 in Severe or Moderately Severe Hemophilia B Patients

Adjusted ABR for Lead-in and Post-Treatment period was estimated from a repeated measures generalized estimating equations negative binomial regression model accounting for the paired design of the trial with an offset parameter to account for the differential collection periods. Treatment period was included as a categorical covariate.

One-stage activated partial thromboplastin time (aPTT) based endogenous FIX activity levels from central laboratory assay.

Annualized consumption of FIX replacement therapy.

Adjusted ABR for Lead-In and Post-Treatment period was estimated from a repeated measures generalized estimating equations negative binomial regression model accounting for the paired design of the trial with an offset parameter to account for the differential collection periods. Treatment period was included as a categorical covariate.

Adjusted ABR for Lead-In and Post-Treatment period was estimated from a repeated measures generalized estimating equations negative binomial regression model accounting for the paired design of the trial with an offset parameter to account for the differential collection periods. Treatment period was included as a categorical covariate.

Adjusted ABR for Lead-In and Post-Treatment period was estimated from a repeated measures generalized estimating equations negative binomial regression model accounting for the paired design of the trial with an offset parameter to account for the differential collection periods. Treatment period was included as a categorical covariate.

One-stage aPTT-based endogenous FIX activity levels from central laboratory assay.

One-stage aPTT-based endogenous FIX activity levels from central laboratory assay.

A target joint was defined as 3 or more spontaneous bleeding episodes into a single joint within a consecutive 6-month period prior to the dosing visit and which was not resolved by the time of dosing. An identified target joint with ≤2 spontaneous bleeding episodes within a consecutive 12-month period was considered resolved.

The iPAQ was designed to provide an evaluation of daily physical activities in metabolic equivalent of task (MET) minutes/week. To calculate MET minutes a week multiply the MET value given (walking = 3.3, moderate activity = 4, vigorous activity = 8) by the minutes the activity was carried out and again by the number of days the activity was undertaken. A higher score is considered to be more favorable.

The EQ-5D-5L descriptive system of health-related QoL states consists of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). The EQ-5D-5L VAS overall score ranges from 0 to 100. A higher score is considered to be more favorable.

To monitor participants for liver fibrosis and potential occurrences of liver malignancies, abdominal ultrasounds were performed. Number of participants with change in abdominal ultrasound result from normal to abnormal, abnormal to abnormal (no change) and missing to abnormal are reported for this outcome measure.

Number of participants who developed antibodies directed against AAV5 (including IgM, IgG and neutralizing antibodies) are reported for this outcome measure. A participant was reported as having an IgG and IgM anti-AAV5 antibody titer greater than or equal to (≥) the LOD if both the screening and confirmatory test results were positive and the titer value was ≥ 50.

Number of participants with >LOD level of fix inhibitors up to Month 60 are reported for this outcome measure. Here, LOD = 0.415 Nijmegen-Bethesda Units per milliliter (NBU/mL).

Number of participants with increased AST and ALT levels and who used corticosteroids to treat these elevations are reported for this outcome measure.

Only parameters with post-baseline, newly occurring or worsening potentially clinically significant laboratory values are reported for this outcome measure.

Criteria threshold:

Hemoglobin: < 80 grams per liter (g/L); Platelet Count: < 50 10^9 cells per liter; AST and ALT: > 2 x Baseline value; Total Bilirubin: > 2 x upper limit of normal (ULN).

A participant was considered to no longer be shedding vector DNA if they had a negative laboratory result (<LOD) for 3 or more consecutive timepoints.

Inflammatory markers assessed included Interleukin-1beta (IL-1β), Interleukin-2 (IL-2), Interleukin-6 (IL-6), Interferon gamma (IFNγ), and Monocyte chemotactic protein-1 (MCP-1).

Lower limit of quantification (LLOQ): IFNγ = 2.86 nanograms per milliliter (ng/mL), IL-1β = 0.60 ng/mL, IL-2 = 0.72 ng/mL, IL-6 = 0.94 ng/mL, MCP-1 = 1.68 ng/mL.

Number of participants with inflammatory markers >= LLOQ are reported for this outcome measure.

Number of participants with AFP levels >= LLOQ at Month 60 are reported for this outcome measure. LLOQ for AFP = 1.09 IU/mL.